The experiments are designed to study further the biology and repair capabilities of the fibrocartilaginous knee joint meniscus and provide important data regarding fundamental aspects of the cell biology of fibrocartilage as a tissue. The specific aims of the project are to utilize our recently developed organ culture model to: (1) determine the role of various substances, such as fibronectin, collagen type I, and TGF-beta, on in vitro meniscal repair; (2) determine the role of synoviocytes in meniscal wound healing; (3) determine the ability of a non-physiologic matrix (agarose) to act as a scaffolding to support meniscal repair in vitro; and (4) develop an in vitro animal model to study meniscal repair based on the results of the previous aims. Additionally, studies to elucidate the structure of the core protein of rabbit meniscal proteoglycans and bovine lubricin, the lubricating glycoprotein of synovial fluid, will be continued. To achieve these goals the following methodologies will be used: (1) cell and organ culture techniques; (2) histological techniques to include light and electron microscopy; (3) conventional and high-pressure liquid chromatography; (4) SDS-polyacrylamide and agarose gel electrophoresis; (5) autoradiography; (6) morphometry and immunohistochemistry; (7) in vitro cell free mRNA translation; (8) oligodeoxynucleotide probe synthesis; and (9) preparation and screening of cDNA libraries. Data obtained from the proposed experiments on meniscal wound healing will provide a basis for future applications to clinical orthopaedic practice. Ultimately the animal models may pave the way for human trails in an effort to obviate the need for meniscectomies and their morbid sequalae. Data obtained from the experiments on meniscal proteoglycans and lubricin will provide important insights into the structure of these molecules and provide a basis for future studies designed to more clearly and specifically elucidate the way in which these molecules aid fibrocartilaginous meniscus in performing its functional role as a tissue. Thus, insights gained from the proposed research can be expected to further our understanding of synovial joint physiology and thereby aid in design and selection of treatment modalities to be used by the clinican.